Preparation of methyl 4-oxobutyrate



Patented Apr. 17, 1951 PREPARATION OF METHYL 4-OXOBUTYRATE William F.Gresham, Richard E. Brooks, and Walter M. Bruner, Wilmington, Del.,assignors to E. I.-du Pont de Nemours- & Company, Wilmingtn, Del., acorporation of Delaware No Drawing Application July 3, 1947, rl,

Serial No. 758,984 r 3 Claims. (Cl. 260483) 'This invention relates tothe synthesisof orcase is a continuation in part of our copendingapplication S. N. 598,208,1'iled June '7, 1945, now

Patent No. 2,437,600.

It .was earlyobserved by Patart (French Patent 593,648) that when amixture. containing ethylene, carbon monoxide, and hydrogen was heatedunder a pressure of 150 to 250 atmospheres at a temperature-of 300 C. inthe-presence of a zinc chromate catalyst, a reaction'jproduct wasobtained which consisted essentially of methanol andhydrocarbons, butwhich also'con tained very small quantities of'aldehyde's 'and' higheralcohols; In 1930, it was-reported by Smith, Hawk, and Golden (J. A. C.S., 52, 3221) that oxygen containing compounds' other than methanol wereformed in 25% to 35% yield when mixtures of ethylene, carbon monoxide,and hydrogen were heated at temperatures of about 206.

to 245. C., under atmospheric pressure in the presence of acobalt-copper-manganese oxide catalyst. The nature of theseoxygen-containing compounds was not ascertained, although aldehydesboiling below 100 C. were shown 'to be present. Later it was reported(German Patents 539,990 and 660,619) that mixtures of hydrogen andcarbon monoxide react with ethylene at high temperature (500" C.) underincreased pressures (150 atmospheres to give a mixture of hydrocarbons,higher alcohols, and ketones. More recently, an important advance wasmade by O. Roelen (U. S. Patent 2,327,066) who found that yields ofpropionaldehyde considerably higher than had been obtained theretofore(in one instance, the amount of propionaldehyde reported by Roelen was40% of the total weight of liquid product), and, in addition, otheroxygen-containing products, could be obtained by processing mixturesofethylene, carbon monoxide, and hydrogen at a temperature of about 40 to200 C.

under a pressure within the range of about 20 to 300 atmospheres in thepresence of hydrogenation catalysts.

An object of this invention is to provide an improved process for thesynthesis of saturated and unsaturated aldehydes from organicunsaturated compounds containing olefinic unsaturation, carbonmonoxidaand hydrogen. Another object is to control the reaction betweenolefinic compounds, carbon monoxide and hydrogen so as to obtainaldehydes almost exclusively, rather than the mixture of ketones,aldehydes, etc., ob.- tained according to the prior art. Other objectswill appear hereinafter: v

This invention involves the surprising dis-.. covery that at'pressuresin excess of 300 atmose: pheres, the formation of ketones from comt-zpounds containing olefinic unsaturation, carbon monoxideand hydrogen, inthe presence of hydrogenation catalysts is completely or almostcompletely avoided, and aldehydes are formed in very high yields. beenbeen-discovered in accordance with the in'-. vention that the reactionbetween olefinic ,compounds, carbon monoxide, and hydrogen producesaldehydes in yields as high as to 100% at pressures in excess of 300atmospheres, prefer,- ably within the range of about 325 to 1500 atmos-I pheres, at a temperature of about to 250 C;

preferably to 200 C., in the presence of certain catalysts to behereinafter disclosed.

In one of its important aspects the invention may be viewed as a'novelmethod for controlling competing reactions in the olefineHzCO system, sothat the desired aldehydic Products are obtained selectively. Thus, in aspecific embodiment, the present invention involves two competingreactions, e. g., 1 CHZ=CHZ 00 H, on ornono According to the prior artthese tworeactions (and others) occur simultaneously at pressures. up to300 atmospheres. The normal effect of in- More particular1y,'it has 3creased pressure would be to suppress reaction (1) and to favor reaction(2 since the former is accompanied by the smaller volume decrease.

The following table, based on experimental data obtained by proceduresdescribed more fully in the examples which follow, shows the effect ofpressure on these competing reactions. Briefly, the experiments weremade by heating mixtures containing 75 cc. diethyl ether, 28 grams ofethylene and 10 grams of metallic cobalt catalyst in a shaker tube inthe presence of a gas containing two volumes of hydrogen per volume ofcarbon monoxide. Temperatures were held within the range of 120 to 160C. The reaction was exothermic, and a heat-removing means was required,especially at the higher pressures. The table shows that at pressuresabove about 300 atmospheres, propionaldehyde formation was selectivelyfavored.

Reaction between ethylene, hydrogen and carbon monoxide Weight ofPropiht 5 0th Reaction onaldehyde 91 Pressurg Time (Monomer and g g g itrimcr) obtained g 0 uc Atm. Min. Grams Grams 200 66 4. 6 4. 4 280 60 4.7 10. 4 350 71 35 14. 8

This advantage is observed not only with ethylene, but with the olefiniccompounds generally. A further advantage of employing increasedpressures is realized when the olefinic reactant is propylene, for thereaction at pressures above 300 atmospheres yields a butyraldehydefraction which contains a much higher ratio ofn-butyraldehyde:isobutyraldehyde than the corresponding product obtainedat pressures below 300 atmospheres.

The effect of pressure in selectively favoring aldehyde formation isverypronounced when the molar ratio of CO H2 is initially from about 121.5to about 1:10. These improved results are realized not only withrelatively stable olefines such as ethylene, but also with olefinicmaterials which polymerize rapidly, such as the dienes, although loss bypolymerization of the reactant, when the latter type of olefinicmaterials isused, is sometimes encountered. Such loss may be reduced,however, by the use of inhibitors like hydroquinone.

The unsaturated compounds containing olefinic unsaturation which may beused in accordance with this invention are the olefinic hydrocarbons andother organic compounds containing a ,(i. e., at least one).non-benzenoid double bond between carbon atoms. Suitable examples ofsuch compounds are the olefinic hydrocarbons themselves, e. g. ethylene,alkyl-substituted ethylenes (such as propylene, butene-2, isobutylene,pentene-l, tetramethyl ethylene, diisobutylene, and cracked gasolinefractions), cyclohexene, butadiene, isoprene, polymerized dienes,styrene, alpha-methyl styrene, vinyl cyclohexene, pinene, limonene,mixed olefines or olefine fractions obtainable by cracking and/ordehydrogenation of petroleum, cyclohexadiene, dicyclopentadiene;unsaturated oxygenated compounds such as allyl alcohol, allyl acetate,allyl ethers, methallyl alcohol, vinyl acetate, furan, methylmethacrylate, methyl acrylate, methallyl propionate, methyl oleate,methyl vinyl ketone, methyl vinyl ether,

cyclohexene carboxylic acids, esters of cyclohexene carboxylic acids(such as methyl M-tetrahydro benzoate) methallyl methacrylate, acrolein;and, in general, the unsaturated hydrocarbons, alcohols, nitriles,esters, ethers, carboxylic acids, amides, aldehydes and ketonescontaining non-benzenoid olefinic unsaturation. Compounds of the formulaRX, having not more than 9 carbon atoms per molecule, X being a memberof the class consisting of -COOH, -CN and -COO alkyl groups and R. beingan olefim'c hydrocarbon radical, are especially suitable.

The olefinic reactants employed in the practice of this invention shouldpreferably be deoxidized prior to use.

The catalysts which may be employed include the hydrogenation catalystsgenerally, such as nickel, cobalt, iron, copper, ruthenium, and the likeand mixtures or compounds thereof. These materials may be used incombination with each other or with inert materials, such as kieselguhr,pumice, etc., or promoters such as ThOz, Mn, etc. The amount of catalystemployed is generally about 0.1 to 10.0% based on the total Weight ofthe reaction mixture.

- The reaction is preferably conducted by heating a mixture of carbonmonoxide, hydrogen, and organic compound containing olefinicunsaturation in a suitable pressure-resistant vessel in the presence ofone of the aforesaid catalysts. Maximum pressure is limited only by thestrength of the retaining vessel and may be as high 'as 3000 atmospheresor even higher. The reaction may be conducted either batchwise orcontinuously. The relative proportions of reactants employed may bestoichiometricallyrequired quantities, al-' though other proportions maybe employed if desired. Excellent results are obtained when the molalratio of CO 1H2 :olefineis in the range of 1:2c-1to about 1:4:1,but'such an excess of hydrogen is not indispensable In one method ofpracticing the invention the olefinic compound, catalyst, and solventare placed in a pressure ves sel, and a mixture of carbon monoxide andhydrogen. is injected under 'very high pressure. After the reaction iscomplete, the resulting liquid product is removed from the reactionvessel and the aldehydes are separated therefrom by any suitable method,such as by fractional distillation. In some instances, the productcontains the desired aldehydes in polymeric (particularly trimeric)form, and such products may be readily. depolymerized duringdistillation to obtain the monomers.

If desired, any inert liquid may be employed as a reaction medium.vMoreover, it has been discovered that in certain cases the yield ofproduct obtained and, in fact, the nature and rate of the reactionsoccurringare determined at least in part by the nature of the reactionmedium, when a medium is employed. Thus, if water is employed, thereaction yields relatively large amounts of unsaturated aldehydes.Examples of suitable solvents for the formation of saturated aldehydesare cyclohexane, xylene, methyl formate, and diethyl ether.

The advantages of the present invention reside not only in the very highyields of aldehydes obtained with'such olefines as ethylene, but also inthat it permits the preparation of aldehydic products from olefinicreactants which do not give appreciable yields of aldehydes at lowerpressures. In many instances, the aldehydes thus obtained can behydrogenatedin situ to the corresponding primary alcohols.' Formation ofket n s, or p oductsderired, thereiromis vir--...:-

Example 1.-The following table shows the .efiect of pressure, and theproportion of hydrogen in the reaction mixture, onthe reaction be tweencarbon monoxide, hydrogen and ethylene. .In each experiment the reactionmixture was passed over reduced fused cobalt catalyst at a temperatureof 140 to 150 C. (continuous process) and the resulting liquid productwas distilled for recovery of the oxygen-containing constituents.

ucts having a boiling range of from 96 C. at 8 mm. to 158 C. at 7 mm.

v [The carbonyl number is the number of milli-' grams of KOH per gram ofsample, required to neutralize the acid liberated by reaction betweenthe material tested and hydroxyl amine hydrochloride.

Example 7.-A mixture containing 82.1 grams (1.0 mol) of cyclohexene, 75cc. of diethylether I and 10 grams of reduced, fused, cobalt catalystcontaining 3% copper was processed-in a copperlined shaker tube for 2hours, under a pressure ."Example 2.A mixture containing 10 grams hoursat a temperature of 108 to 120 C. under a pressure' of 470 to 790atmospheres with CO I 2H2. Distillation of the resulting product gave69.9 grams of n-butyraldehyde which corresponds to a conversion of97.1%. A portion of the product was in the form of trimer, whichdepolymerized during the distillation.

Example 3.A mixture containing 140 grams of ethylene, 140 grams ofcarbon monoxide and 20 grams of hydrogen was pumped through asilver-lined tube 20 inches long (inside diameter, one inch) at atemperature of 140 C. under a pressure of 700 atmospheres (time onehour). The reaction vessel contained 65 cc. of metallic cobalt catalyst,8 to 14 mesh; arranged in 3 beds separated by copper rivets. Analysis ofresulting products showed that propionaldehyde was produced in 80%conversion, based on the ethylene charged. Rate of production ofpropionaldehyde was 140 pounds per cubic foot of catalyst per hour.

Example sir-Example 3 was repeated exactly except that the reactionmixture also contained 900 grams of cyclohexane. The conversion ofethylene to propionaldehyde was 90%. Rate of production ofpropionaldehyde was 180pounds per cubic foot of catalyst per hour. I

Example 5.-'A mixture containing 128 cc. cyclohexane, 28 grams ofethylene and 10 grams of copper molybdate catalyst was heated for 3hours at155 to 165 C. under 605 to 810 atmospheres of CO 21-12. Theresulting reaction prod uct contained substantially no diethyl k etone,w

grams of unidentified aldehydecontaining prodof 580 to 790 atmospheresof CO 41-12 at a temperature of 110 to 112 C. Distillation of resultingproducts gave 41.5 grams of hexahydrobenzaldehyde, B. P. 55 to 60 C. at19 to 20 mm. (Carbonyl No. 507.5, 508.1; calc., 501), 11.8 gramshigh-boiling products (103/7 mm.-194/5 mm.) and 8.6 grams of adistillation heel which appeared to be about half hexahydrobenzaldehydetrimer. 1

Example 8.-'A'mixture containing 58.8 grams (0.716 mol) of cyclohexene,75 cc. of cyclohexane and 10 grams of a reduced, fused, cobalt catalystwas processed in a copper-lined shaker tube for 2 hours. Sufficient COand Hzin the mol ratio of 15 4 was injected to maintain the pressure of183 to 196 atmospheres at the operating temperature of 160 to 170 C.Distillation of the resulting product at atmospheric pressure gave 93.3grams of a mixture of cyclohexane and unconverted cyclohex ene (B. P. 81to 83 C.) (cyclohexene content, about 41 grams), and 3.9 grams of impurematerial boiling in the range of 66 C./18 mm. to 81 C./2 mm. (CarbonylNo. of 196). There remained only 0.9 gram of distillation heel. Thisexperiment, when compared with the experiment described in Example 7,shows the poor conversion obtained a 4-oxobutyrate in 57.4% yield, B. P.62 C. at 10 mm. This material was identified by hydrogenation totetramethylene glycol (copper chromite catalyst, ca. 230 C., 700atmospheres).

Example 10.-A mixture containing cc. of

diethyl ether, 20 grams of reduced, fused cobalt catalyst and 44 gramsof butadiene was heated ina shaker tube for 2 hours at 142 to 220 C.under a pressure of 400 to 575 atmospheres of CO H2. Distillation of theresulting product under atmospheric pressure gave 11.4 grams of fractionwhich boiled within the range of 101 to 121 C., having a Carbonyl No. of449.

Example 11.-'-A mixture containing cc. of

catalyst and 28 grams of ethylene was heated for 1.5 hours at to 176 C.under a CO 2H2 pressure of 550 to 730 atmospheres in a stainless steelshaker tube. Distillation of the product gave 13.3 grams ofpropionaldehyde (B. P., 49 C'.) and 15grams ofalpha-methyl-beta-ethylacrolein (B. P. water azeotrope, 94 C.; B. P.,after separation from water, to 139 C.)

' Example 12.-The following table recordsa se- 7 ries of experimentswhich show the reaction of' various olefinic'compounds with carbonmonoxide and hydrogen in shaker tubes under the condi tions stated(reaction time 0.5 to 2.0 hour s) ,1 p

Approi Temper- Pressure, Olefinic Compound Catalyst ature, Atmos-Product 00.13:! c O pheres 1e 1 Per cent ililyl cyanideCobalt(cyclohexane=dilu- 1:1' 130 630-750 Nc cH. .cHo as out MethylN-tetrahydo 1:1 165185 600-750 Methyl formyl hexahydrobenzoate (B. P.73- 70 drobenzoate. 78 0., 3 mm). Furan dn 1:2 100-205 255-740 Mixtureof aldehydes and alcohols (tetra-hydro .iurfuryl alcohol identified)-Tetramethylethyldo 1:2 130-140 600-775 Mizitulrle 1containing highboiling aldehyde and ene. a co s. Allyl acetateCobalt)(methylformate;dil- 1:2 140-148 750-775 CH3CO(CH2)4OH (B. F, 80 2mm.) 39 uent Methyl olcatenm do 122 140-145 600-750 Mixed aldehydeestersl; 72 Vinyl cyclohexene do 1:2 120-134 475-720 Mixed monoanddialdehydes 65 j, Example 13.-A mixture containing 56.1 grams ofbutene-2, 100 cc. methyl formate, and 10 grams of reduced, fusedalkali-free cobalt catalyst was heated in a silver-lined shaker tube for2 hours at 120 to 175 C. under a CO 21-12 pressure of 460 to 770atmospheres. Distillation of the combined products of two such runs gave110.3 grams of (CI-I3) (C2H5)CHCHO (B. P. 54 C. at 200 mm.), whichcorresponds to a conversion of 64%.

Example 14. A mixture containing 75 cc. of diethyl ether, 28 grams ofethylene and 10 grams of a reduced, fused, alkali-free cobalt catalystcontaining 3% copper was heated in a copper-lined shaker tube with a gascontaining 2 volumes of hydrogen per volume of carbon monoxide under apressure of 450 to 780 atmospheres at a temperature of 110 to 120 C. for1.8 hours. The resulting product was Withdrawn from the reaction vessel,and ether was removed therefrom by fractional distillation. A residue ofpropionaldehyde (B. P., 46 to 48 C.) and propionaldehyde trimer (B. P.,65 C. at 12.5 mm.; refractive index (25 0., D line):1.4110) remained.The latter was depolymerized by distillation in the presence of a fewdrops of sulfuric acid. The total weight of propionaldehyde obtained was42.8 grams which corresponds to a conversion of 73.8%.

Example 15. A mixture having the composition 4H2 CO Cal-ls was passedover metallic c0- balt catalyst (contact time, 0.8 min.) at 700atmospheres pressure at a temperature of 170 C. Distillation of theliquid product showed that 65% of the propylene had reacted, forming aproduct which was chiefly a mixture of normal and isobutyraldehydes. Therelative amounts of n-butyraldehyde and isobutyraldehyde were 7 and 25%respectively. Repetition of the experiment with H2 2C0 Cal-Ia at 500atmospheres pressure also gave a fraction containing butyraldehydes. Therelative amounts of n-butyraldehyde and isobutyraldehyde in thisfraction were 56% and 44% respectively.

While, in the foregoing examples, the invention is illustrated as amethod for the preparation of saturated and. unsaturated aldehydes, itwill be understood that the method can be adapted to the manufacture ofother organic compounds derivable therefrom. For example, condensationproducts of such aldehydes are as produced from the unsaturatedcompound, carbon monoxide, and hydrogen may be converted to cyclictrimers or high-boiling products under the reaction conditions. Also, ifthe hydrogenation is prolonged, it is possible to convert thealdehydes'to the corresponding alcohols. Alternatively, the aldehydesmay be hydrogenated to the corresponding alcohols in a separate step, inthe absence of carbon monoxide. At temperatures above about 180 to 190C., hydrogenation of carbon monoxide readily occurs and the alcoholsproduced tion vessels lined with silver or copper.

either by CO hydrogenation, or by aldehyde hydrogenation,- may reactwith aldehydes simultaneously formed, so that the resultant product maycontain acetals.

The invention may be practiced by heating the reactants in any suitablepressure-resistant ves sel such as an autoclave or tubular converterpreferably made of or lined with inert materials such as glass,porcelain, inert metals and the like. If desired, materials ofconstruction yielding small amounts of metallic carbonyls which areeffective as catalyst may be employed. Outstanding results, however, areobtained in reac- In the continuous process, the reactants may beintroduced at one or more points within the reaction vessel if desired.In certain instances, it is preferred to employ a tubular reactionvessel in which the temperature and pressure are not uniform throughoutthe length of the vessel.

Generally, mixtures containing carbon monoxide and hydrogen in theproportions of about 1:2 to 1:4 are preferably employed in the practiceof the invention, but other mixtures of carbon monoxide and hydrogen,containing inert gases in certain instances, may be utilized if desired.The use of an excess of one of the reactants or of an inert diluent gasassists in dissipating the heat of the reaction.

The products obtained in accordance with this invention arewidelyuseful, and are especially valuable as intermediates for themanufacture of alcohols, glycols, esters, and numerous other materials.

Since many embodiments of the invention may be made without departingfrom the spirit and scope, it will be understood that we do not limitourselves except as set forth in the following claims.

We claim:

1. A process for preparing methyl 4-oxobutyrate which comprises heatingmethyl acrylate with carbon monoxide and hydrogen, the initial molalratio of CO 2 H2 being from about 1:15 to about 1:10, at a temperaturewithin the range of to 250 C. under a pressure of 325 to 1500atmospheres in the presence of a cobalt-containing hydrogenationcatalyst whereby a product containing methyl l-oxobutyr'ate is produced.

2. A process for preparing methyl l-oxobutyrate which comprises heatingmethyl acrylate with carbon monoxide and hydrogen, the initial molalratio of CO He being from about 121.5 to about 1:10, at a temperature ofto 167 C. under a pressure of 390 to 730 atmospheres in the presence ofa. cobalt-containing hydrogenation catalyst whereby a product containingmethyl 4-oxobutyrate is produced.

3. A process for preparing methyl 4-oxobutyrate which comprises heatingmethyl acrylate and a. hydroquinone inhibitor with carbon monoxide andhydrogen, the initial molal ratio of CO H2 being from about 1:15 toabout 1:10, 5

at a temperature of 145 to 167 C. under a pressure of 390 to 730atmospheres in the presence of a cobalt-containing hydrogenationcatalyst whereby a product containing methyl 4-oxobutyrate is produced.

WILLIAM F. GRESHAM. RICHARD E. BROOKS. WALTER M. BRUNER.

REFERENCES CITED UNITED STATES PATENTS J Name Date Roelen Aug. 17, 1943Number

1. A PROCESS FOR PREPARING METHYL 4-OXOBUTYRATE WHICH COMPRISES HEATINGMETHYL ACRYLATE WITH CARBON MONOXIDE AND HYDROGEN, THE INITIAL MOLALRATIO OF CO: H2 BEING FROM ABOUT 1:15 TO ABOUT 1:10, AT A TEMPERATUREWITHIN THE RANGE OF 75* TO 250* C., UNDER A PRESSURE OF ACOBALT-CONATMOSPHERES IN THE PRESENCE OF A COBALT-CONTAININGHYDROGENATION CATALYST WHEREBY A PRODUCT CONTAINING METHYL 4-OXOBUTYRATEIS PRODUCED.